Title : Structure and biological function of
ENPP6 , a
choline-specific glycerophosphodiester-phosphodiesterase
Abstract :
- Choline is an essential nutrient for all living cells and is produced extracellularly by sequential degradation of phosphatidylcholine (PC)
- However, little is known about how choline is produced extracellularly
- Here, we report that ENPP6 , a choline-specific phosphodiesterase , hydrolyzes glycerophosphocholine ( GPC ), a degradation product of PC, as a physiological substrate and participates in choline metabolism
- ENPP6 is highly expressed in liver sinusoidal endothelial cells and developing oligodendrocytes, which actively incorporate choline and synthesize PC
- ENPP6-deficient mice exhibited fatty liver and hypomyelination, well known choline-deficient phenotypes
- The choline moiety of GPC was incorporated into PC in an ENPP6-dependent manner both in vivo and in vitro
- The crystal structure of ENPP6 in complex with phosphocholine revealed that the choline moiety of the phosphocholine is recognized by a choline-binding pocket formed by conserved aromatic and acidic residues
- The present study provides the molecular basis for ENPP6-mediated choline metabolism at atomic, cellular and tissue levels